Naïve T cells re-distribute to the lungs of selectin ligand deficient mice

15Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

Abstract

Background: Selectin mediated tethering represents one of the earliest steps in T cell extravasation into lymph nodes via high endothelial venules and is dependent on the biosynthesis of sialyl Lewis X (sLex) ligands by several glycosyltransferases, including two fucosyltransferases, fucosyltransferase-IV and -VII. Selectin mediated binding also plays a key role in T cell entry to inflamed organs.Methodology/Principal Findings: To understand how loss of selectin ligands (sLex) influences T cell migration to the lung, we examined fucosyltransferase-IV and -VII double knockout (FtDKO) mice. We discovered that FtDKO mice showed significant increases (,5-fold) in numbers of naïve T cells in non-inflamed lung parenchyma with no evidence of induced bronchusassociated lymphoid tissue. In contrast, activated T cells were reduced in inflamed lungs of FtDKO mice following viral infection, consistent with the established role of selectin mediated T cell extravasation into inflamed lung. Adoptive transfer of T cells into FtDKO mice revealed impaired T cell entry to lymph nodes, but selective accumulation in non-lymphoid organs. Moreover, inhibition of T cell entry to the lymph nodes by blockade of L-selectin, or treatment of T cells with pertussis toxin to inhibit chemokine dependent G-coupled receptor signaling, also resulted in increased T cells in non-lymphoid organs. Conversely, inhibition of T cell egress from lymph nodes using FTY720 agonism of S1P1 impaired T cell migration into non-lymphoid organs. Conclusions/Significance: Taken together, our results suggest that impaired T cell entry into lymph nodes via high endothelial venules due to genetic deficiency of selectin ligands results in the selective re-distribution and accumulation of T cells in non-lymphoid organs, and correlates with their increased frequency in the blood. Re-distribution of T cells into organs could potentially play a role in the initiation of T cell mediated organ diseases. © 2010 Harp, Onami.

Cite

CITATION STYLE

APA

Harp, J. R., & Onami, T. M. (2010). Naïve T cells re-distribute to the lungs of selectin ligand deficient mice. PLoS ONE, 5(6). https://doi.org/10.1371/journal.pone.0010973

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free